Poly(lactic-co-glycolic acid) Bone Scaffolds with Inverted Colloidal Crystal Geometry MEGHAN J. CUDDIHY, M.S., 1 and NICHOLAS A. KOTOV, Ph.D. 1–3 ABSTRACT Controllability of scaffold architecture is essential to meet specific criteria for bone tissue engineering implants, including adequate porosity, interconnectivity, and mechanical properties to promote bone growth. Many current scaffold manufacturing techniques induce random porosity in bulk materials, requiring high porosities (>95%) to guarantee complete interconnectivity, but the high porosity sacrifices mechanical properties. Additionally, the stochastic arrangement of pores causes scaffold-to-scaffold var- iation. Here, we introduce a biodegradable poly(lactic-co-glycolic acid) (PLGA) scaffold with an inverted colloidal crystal (ICC) structure that provides a highly ordered arrangement of identical spherical cavities. Colloidal crystals (CCs) were constructed with soda lime beads of 100-, 200-, and 330-lm diameters. After the CCs were annealed, they were infiltrated with 85:15 PLGA. The method of construction and highly ordered structure allowed for ease of control over cavity and interconnecting channel diameters and for full interconnectivity at lower porosities. The scaffolds demonstrated high mechanical properties for PLGA alone (>50 MPa), in vitro biocompatibility, and maintenance of osteoblast phenotype, making them promising for a highly controllable bone tissue engineering scaffold. INTRODUCTION B ONE TISSUE ENGINEERING aims to replace traditional au- tograft and allograft repair strategies with the implan- tation of mechanically functional biodegradable constructs that support the wound site and hasten the body’s natural repair mechanism until bone has filled the defect. 1,2 A number of structural criteria for implantable scaffolds are agreed upon, including sufficient porosity, interconnectivity, and mechanical properties. Porosity and complete inter- connectivity throughout a scaffold are necessary to promote uniform cell loading and migration, eventual tissue and vasculature ingrowth, and sufficient nutrient diffusion and interstitial fluid and blood flow. 3,4 The ideal bone tissue engineering scaffold should have a precisely designed struc- ture that provides complete interconnectivity of pores and maximum load bearing capacity. 5 Traditional scaffold fabrication techniques, such as par- ticulate leaching, gas foaming, emulsion freeze-drying, electrospinning, and thermally induced phase separation, are based upon bulk material alteration that yields a random pore structure. 6–10 The random pore distribution risks in- sufficient scaffold interconnectivity and permeability; con- sequently, scaffold porosities often approach 95% to ensure complete interconnectivity throughout the scaffold. Such high porosities present a dilemma in bone tissue engineer- ing, where greater porosity enhances interconnectivity but denies the scaffold sufficient mechanical strength to sup- port the load of the body until tissue regeneration is com- plete. Therefore, there is a need for structural engineering of bone scaffolds, providing sufficient control over three- dimensional (3D) geometry. 11,12 A systematic approach to this problem would be the preparation of well-ordered porous materials with tunable geometry. Computational Departments of 1 Chemical Engineering, 2 Materials Science and Engineering, and 3 Biomedical Engineering, University of Michigan, Ann Arbor, Michigan. TISSUE ENGINEERING: Part A Volume 14, Number 10, 2008 # Mary Ann Liebert, Inc. DOI: 10.1089/ten.tea.2007.0142 1639